rs3755486

Variant names:

• chr2-174767158-C-T
• rs3755486
• ENST00000442996.1:n.322-5591C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636168.2(CHRNA1):​c.-446-7525G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,962 control chromosomes in the GnomAD database, including 11,745 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11745 hom., cov: 31)
• Consequence: CHRNA1 ENST00000636168.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534

Genes affected

ENSG00000236449 (HGNC:):

CHRNA1 (HGNC:1955): (cholinergic receptor nicotinic alpha 1 subunit) The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000236449	ENST00000442996.1	n.322-5591C>T		intron_variant	Intron 3 of 3	1
CHRNA1	ENST00000636168.2	c.-446-7525G>A		intron_variant	Intron 2 of 9	5		ENSP00000490338.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54564 AN: 151846 Hom.: 11752 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.359 AC: 54559 AN: 151962 Hom.: 11745 Cov.: 31 AF XY: 0.355 AC XY: 26393 AN XY: 74266

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.405

Alfa AF: 0.452 Hom.: 9405

Bravo AF: 0.348

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3755486; hg19: chr2-175631886;